Abstract Background Benefits of the stay-at-home order imposed in Italy to prevent SARS-CoV-2 transmission need to be weighed against its impact on citizens’ health. In a country with a solid familial culture and where welfare relies on households, confinement drastically decreased support provided by elder relatives, which may have worsened mental health. Methods A web-based cross-sectional study (LOST in Italy) was conducted on a representative sample of Italian adults during lockdown (27th of April-3rd of May 2020). We asked 3156 subjects to report on reduced help in housework and childcare from retired parents to assess confinement impact on mental health through validated scales before and during the lockdown. Results Overall, 1484 (47.0%) subjects reported reduced housework help from parents, and 769 (64.0%, of the 1202 subjects with children) diminished babysitting support. Subjects reporting reduced housework help had worsened sleep quality (multivariate odds ratio, OR 1.74, 95% confidence interval, CI 1.49-2.03) and quantity (OR 1.50, 95%CI 1.28-1.76), depressive (OR 1.32, 95% CI 1.14-1.53) and anxiety symptoms (OR 1.53, 95%CI 1.32-1.78), compared to those reporting unreduced help. Worsening in sleep quality (OR 2.32, 95%CI 1.76-3.05) and quantity (OR 1.80, 95%CI 1.36-2.37), depressive (OR 1.79, 95%CI 1.39-2.31) and anxiety symptoms (OR 1.90, 95%CI 1.48-2.46) was also associated with reduced babysitting help. In subjects with poorer housing and teleworking, mental health outcomes were worse. Conclusions Confinement came along with reduced familial support from parents, negatively impacting mental health. Social networks and support within families provided by older relatives act as a resilience factor and a potential vulnerability that affects mental health outcomes. Health and social services response should be designed to address mental health needs and mitigate long-term health costs caused by the pandemic's unprecedented stressfulness and unknown duration. Key messages

In 2018, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) reported the appearance of new psychoactive substances (NPS) on European Union (EU) at a rate of about one per week for a total of 55 new drugs detected in 2018. On one hand, this figure is similar to that communicated in 2017 (N=51) and both of them are significantly lower if compared to those, above one hundred, appeared in 2014 and 2015. On the other hand, it has to be underlined that there has been a change in the type of substances coming into illegal market, since the most recent new psychoactive substances are increasingly more targeted in the long-term and to drug users with more addictive behavior. Specifically, new synthetic opioids and benzodiazepines are now the most reported substances by the EU Early Warning System, together with a distinct range of other recreational substances1. The epidemics of both classes of substances come from United States and Canada, where both caused severe intoxications and fatalities purposely related to the use of synthetic opioids, particularly fentanyl derivatives. Although these two phenomena have not been so diffused in Europe, concerns do exist also in this area. About 50 new synthetic opioids, mainly fentanyl illicit analogs, have been reported up to now to the EU Early Warning System and the seizures of carfentanil, one of the most hazardous and potent opioids, have been particularly alarming2-5. In this latter case and in that of many other fentanyl derivatives, due to the extreme potency of these compounds, they can be trafficked in very small quantities, which are difficult to detect2. In addition, the synthetic opioids and new illegal benzodiazepine share the occurrence that they have been sold as fake kinds of commonly prescribed pain-relievers and antianxiety drugs. Regarding synthetic opioids, the fake OxyContin tablets containing metoxyacetylfentanyl, or fentanyl itself, have been reported by EU early warning system in the last two years6. In case of new benzodiazepines, some of these are trafficked as fake types of Xanax, containing alprazolam or other compounds of the same class but illegally produced and sold, or even containing fentanyl and analogs7. In this concern, the values of accurate and immediately available toxicological and forensic data are crucial8. Indeed, the drug related severe intoxications and fatalities are seldom associated with the consumption of one substance alone. Drug consumption patterns are often characterized by polyconsumption of both classical drugs and NPS. For this reason, without good forensic and toxicological data, new health threats may be underestimated. The major risk, therefore, is that the role of the most toxic NPS, like fentanyl derivatives, in overdose deaths may be missed, especially when they are consumed together with classical psychotropic drugs, such as heroin, or when other newly marketed compounds such as the above reported new benzodiazepines are in place7,9. If on the one hand the EU Member States, particularly in northern Europe, where this new hazard is more diffused (e.g. Sweden or UK), have invested in improving the availability and sensitivity of the toxicological data implementing analytical protocols. On the other hand, in the majority of the remaining countries the pharmacotoxicological laboratories, both in clinical and in forensic, do not have the capacity to detect NPS and/or their metabolites in NPS related intoxications presenting at e.g. emergency departments and fatalities requiring medico-legal examinations10,11. The first striking problem is the unavailability of the reference standards for NPS in many laboratories. Several of these standards, especially in case of the newest NPS and metabolites, are out of the market, or 2019; 23: 6008-6010

Background The transposition of the New Tobacco Product Directive (TPD) 2014/40/UE in Italy entered into force in 2016. Main regulations were: Reporting obligations, ban of some ingredients and of some products with characterising flavours Pictorial warnings with Quitline number Sale ban of 10-cigarette packages Reporting obligations for new electronic-cigarettes (e-cigs); Advertising ban; child - and tamper - proof for refill containers. The transposition was an occasion to add new measures: Stricter enforcement of the sale ban to minors Smoking ban in cars with minors and pregnant women Smoking ban in outdoor areas of Pediatric and Gynecologic Departments Sale ban of e-cig and refill containers to minors Methods Presentation of the evaluation plan of the impact of the new TPD in Italy. Presentation of preliminary results for the year 2017. Results - The behavioural risk factor surveillance system PASSI, the ISTAT survey and the DOXA surveys on representative samples of Italians will allow us to study smoking and e-cigarette prevalence in adults; quitting attempts among smokers; the impact of pictorial warnings on smokers; second-hand smoke exposure in non-smokers; attitudes, perception, and behaviours of Italians after the coming into force of the new TPD; - The GYTS (Global Youth Tobacco Survey) will monitor smoking and e-cig prevalence, tobacco access and availability among Italian adolescents; - the National Institute of Health (ISS) will monitor the compliance with the smoking ban in cars, and the outdoor ban outside some Hospital Departments; - Temporal trend in Quitline calls will be studied. The impact of pictorial warnings will be also studied among smokers calling the Quitline, or attending Italian Smoking Cessation Centers; - The online transmission of ingredients of tobacco products from tobacco companies will be followed at the ISS. We will add preliminary results not yet produced. Conclusions The evaluation plan will allow to study all dimensions of the TPD impact.

Background Heat-not-burn tobacco products are cigarettes heated by an electronic device to generate an aerosol containing nicotine. iQOS is the brand name of such a product by Philip Morris International. It was launched in December 2014 in Italy as a pilot country for the European market. Currently, no information is available on iQOS awareness, use and sales in Italy. Methods We annually conduct a national-wide face-to-face survey on smoking. In order to investigate awareness and use of iQOS, we devoted to heat-not-burn tobacco product a specific section in our 2017 survey. The survey was conducted on a sample of 3086 individuals, who represented the Italian population aged ≥15 years (52.4 million). Official quarter sales data on iQOS were obtained from the Italian Ministry of Health and the relative web search volumes in Italy were retrieved from “Google trends”. Results Among the investigated subjects, 19.5% were aware of iQOS, and 1.4% have tried it. Overall, 1.0% of never, 0.8% of ex- and 3.1% of current smokers have tried iQOS. As regard to e-cigarettes, 2.9% of ex- and 7.7% of current users have tried iQOS. In just one year, iQOS quarter sales were boosted by 17 times from 4.4 tonnes in the early 2016 to 80.0 tonnes in the early 2017, currently representing 0.4% of the whole tobacco market share; Google trends shows similar exponential increase in the relative web search volume. Conclusions Although the share of iQOS in the whole tobacco market is still limited in Italy, we have observed a growing interest in it. Our individual-level data suggest that more than 700 thousand Italians have already tried this tobacco product, including more than 340 thousand never and 50 thousand ex-smokers. Attention should be paid on this emerging phenomenon, which may represent in the near future an impairing gateway to nicotine addiction.

Anabolic Androgenic Steroids (AAS) abuse and misuse is nowadays a harmful habit involving both professional or recreational athletes, as well as general population. AAS are also frequently present in over-the-counter dietary supplements without being declared in the list of ingredients, leaving consumers unaware of the risks of adverse effects. Indeed, health risks of AAS consumption in pharmaceutical preparations or dietary complements seem still underestimated and under-reported. The variety of complications due to AAS misuse involves cardiovascular, central nervous, musculoskeletal and genitourinary systems of both males and females; psychiatric and behavioral effects, damages to metabolic system, skin and mainly liver. For instance, relevant concern has been raised by the AAS hepatotoxicity including adenoma, hepatocellular carcinoma, cholestasis, and peliosis hepatis. The present review reports the information available on the hepatotoxic effects of AAS use in professional and amateur athletes.

According to the most recent World Health Organization report, road accidents represent a very serious public health issue, claiming each year more than 1.2 million lives worldwide and being the leading cause of death among young people aged between 15 and 29 years. Up to now, the policies to reduce this issue are different, unbalanced and often inadequate not only in Italy, but also in the other European Countries. Specifically, the Italian Parliament has recently introduced a new law (n. 41 of March 23rd, 2016), making vehicular homicide together with road traffic injuries a criminal offense, both to be punished as a result of negligence. The measure came into force on March 25th, 2016. In this paper, the provisions of the above-reported law have been assessed, taking into account the modifications introduced in the Penal Code by this law and the impact it is having and will have on drivers on a day-to-day basis. Similarities and differences with legislative framework of some other European countries were also examined. Finally, some open questions to be solved are named as an open eye for future considerations.

Objectives: Studies investigating whether smoking increases or decreases during economic downturn provided contrasting results. For the first time, we used direct questions to analyse changes in smoking behaviour due to the 2008 financial crisis, comparing socio-economic characteristics of smokers who changed with those who kept their smoking intensity.Study design: Cross-sectional survey.Methods: We used data from three annual surveys conducted in Italy in 2012-2014 on representative samples of the Italian general population aged >= 15 years.Results: A total of 1919 current smokers were asked specific questions on the influence of the economic crisis that started in 2008 on their smoking behaviour. Overall, 77.4% of 1919 current smokers reported not to have changed their smoking behaviour, 19.1% to have reduced, and 3.5% to have increased their smoking intensity as a consequence of the economic crisis. The reduction in cigarette smoking increased with age: compared to the respondents aged <25 years, the multivariate odds ratio (OR) for those aged 25-44, 45-64 and >= 65 years were 0.65, 0.46 and 0.33, respectively (P for trend<0.001). Reduction was significantly lower among intermediate (OR = 0.68 compared to low) and high education levels (OR = 0.28; P for trend<0.001). A significant inverse trend for increasing consumption was observed with age (P = 0.022), education (P = 0.003) and family income (P < 0.001).Conclusions: The large majority of current smokers did not change their smoking habit following the economic crisis. However, there are specific vulnerable subgroups of smokers, constituted by the young and subjects with low socio-economic status, that were reactive to the global economic crisis. These groups are more prone to change their smoking behaviours, either for better or -, in a smaller proportion -, for worse. (C) 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

IntroductionAtomoxetine (ATX) is the first non-psychostimulant drug indicated for the treatment of attention-deficit hyperactivity disorder (ADHD) in pediatric patients as an alternative to methylphenidate. The aim of this study was to describe the pharmacokinetic profile of ATX in oral fluid in comparison to plasma in paediatric patients with ADHD.Material and methodsThe protocol was approved by the local research committee. Child’s parent or legal representative signed an informed consent (with assent) before inclusion. Participants were 5 children (2 girls and 3 boys, mean age: 8 y) and 6 adolescents (2 girls and 4 boys, mean age: 14 y) diagnosed as having ADHD and treated with different oral doses of ATX (60, 40, 35, 25, and 18 mg/d). Samples of blood and oral fluid were obtained before and post-dose (along 24 h). Concentrations of ATX and its metabolites 4-hydroxyatomoxetine (4-OH-ATX) and N-desmethylatomoxetine (N-des-ATX) were determined using liquid chromatography–tandem mass spectrometry in plasma and oral fluid.ResultsATX, 4-OH-ATX, and N-des-ATX were found in plasma, but only ATX and 4-OH-ATX were detected in oral fluid samples. Mean ATX was found in plasma and oral fluid at a peak concentration of 589.6 and 19.72 ng/mL with a mean tmax of 1.4 and 2.7 h, respectively. For 4-OH-ATX detected in oral fluid, peak concentration was approximately half that in plasma (7.4 vs 13.8) with a mean tmax of 2.6 h in oral fluid and 2.1 in plasma. A good correlation between ATX and 4-OH-TX in plasma and saliva was achieved.ConclusionThe correlations between ATX and 4-OH-ATX concentrations in the 2 biological fluids indicate that oral fluid concentrations may be an alternative to plasma concentrations.AcknowledgementsSupported by Red de Trastornos Adictivos (ISCIII RTA RD12/0028/0009) and Red SAMID (ISCIII). Esther Papaseit is a Rio Hortega fellow (ISCIII, CM13/00016). IntroductionAtomoxetine (ATX) is the first non-psychostimulant drug indicated for the treatment of attention-deficit hyperactivity disorder (ADHD) in pediatric patients as an alternative to methylphenidate. The aim of this study was to describe the pharmacokinetic profile of ATX in oral fluid in comparison to plasma in paediatric patients with ADHD.

Disclosing chronic use of cannabis has always been a difficult task due to the fact that hair testing of THC alone is not conclusive of use and hair testing of THC-COOH require specific and sensitive instrumentation and laboratory skill, not available for many analytical laboratories. We hypothesized the presence of THC-COOH glucuronide in hair as possible alternative biomarker of repeated consumption of cannabis products. We developed and validated an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method to identify and quantify THC-COOH glucuronide in hair after applying one hour digestion of 25 mg keratin matrix with M3 (Comedical Spa, Italy) reagent at 100°C, using deuterated THC-COOH glucuronide as internal standard. An amount of 10 μl was injected in the ULPC-MS/MS system. Chromatographic separation was carried out on a Acquity UPLC HSS C18 column (2,1 mm × 150 mm, 1.8 μm) using a linear gradient elution with two solvents:0.1% formic acid in acetonitrile (solvent A) and 5 mM ammonium formate pH 3 (solvent B). The flow rate was kept constant at 0.40 mL/min during the analysis. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI). The applied ESI conditions were the following: capillary voltage 1,3 kV, desolvation temperature 600 °C, source temperature 150 °C, cone gas flow rate 20 L/h, desolvation gas flow rate 1000 L/h and collision gas flow rate 0.13 mL/min, cone voltage of 65 V. Following transitions were considered: 521.2→345.03 (Collision energy:16), 521.2 →327.07 (Collision energy: 22),521.2 → 299.09 (Collision energy: 32), with the first one used for quantification. Linear calibration curves were obtained for THC-CCOH glucuronide with correlation coefficients (r2) of 0.99 and a LOQ of 0.1 pg/mg hair. Analytical recovery was between 70.9 and 100.7%. Intra and inter-assay imprecision and inaccuracy were always lower than 10%. No additional peaks due to endogenous substances which could have interfered with the detection of the analytes under investigation were observed in drug-free hair samples. No psychoactive drugs other than the compounds under investigation interfered with the assay. Blank hair samples injected after the highest point of the calibration curve did not present any traces of carryover. The matrix effect in quality control samples ranged from 80 to 101%. Preliminary analysis on 9 different hair samples of consumers disclosed the presence of THC-CCOH glucuronide in the range of 0.30–1.22 pg/mg with by median value of 0.58 pg/mg hair. Simple extraction, identification and quantification of THC-COOH glucuronide in hair by UPLC-MS/MS was developed, validated and tested for its feasibility in clinical samples and provided a good start to consider THC-CCOH glucuronide as alternative hair biomarker of repeated cannabis consumption.

The deleterious effects exerted by prenatal ethanol exposure include physical, mental, behavioural and/or learning disabilities that are included in the term fetal alcohol spectrum disorder (FASD). Objective assessment of exposure to ethanol at both prenatal and postnatal stages is essential for early prevention and intervention. Since pregnant women tend to underreport alcohol drinking by questionnaires, a number of biological markers have been proposed and evaluated for their capability to highlight gestational drinking behaviour. These biomarkers include classical biomarkers (albeit indirect) of alcohol-induced pathology (mean corpuscular volume (MCV), gamma glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) acetaldehyde-derived conjugates, and finally derivatives of non-oxidative ethanol metabolism (fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), ethyl sulphate (EtS) and phosphaditylethanol (PEth)). Since ethanol itself and acetaldehyde are only measured few hours after ethanol intake in conventional matrices such as blood, urine and sweat, they are only useful to detect recent ethanol exposure. In the past few years, the non-oxidative ethanol metabolites have received increasing attention because of their specificity and in some case wide time-window of detection in non-conventional matrices from the pregnant mother (oral fluid and hair) and fetus-newborn (neonatal hair, meconium, placenta and umbilical cord). This article reviews bioanalytical procedures for the determination of these markers of ethanol consumption during pregnancy and related prenatal exposure. In addition, clinical toxicological applications of these procedures are presented and discussed.

Background: Ethanol is the most widely used drug in the world and a human teratogen whose consumption among women of childbearing age has been steadily increasing. There are no Italian or Spanish statistics on ethanol consumption during pregnancy nor any information regarding prevalence of fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD). There is also a reasonable suspicion that these two diseases are underdiagnosed by professionals from the above-reported countries. The objectives of this study were: 1) to evaluate the experience, knowledge and confidence of Italian and Spanish neonatologists and paediatricians with respect to the diagnosis of FAS and FASD, and 2) to evaluate professionals awareness of maternal drinking patterns during pregnancy.Methods: A multiple-choice anonymous questionnaire was e-mailed to Italian neonatologists registered in the mailing list of the corresponding Society and administered to Italian and Spanish paediatricians during their National Congress.Results: The response rate was 16% (63/400) for the Italian neonatologists of the National Society while a total of 152 Spanish and 41 Italian paediatricians agreed to complete the questionnaire during National Congress. Over 90% of the surveyed physicians declared that FAS is an identifiable syndrome and over 60% of them identified at least one of the most important features of FAS. Although over 60% Italian responders and around 80% Spanish responders were aware that ethanol use in pregnancy is dangerous, approximately 50% Italian responders and 40% Spanish ones allowed women to drink sometimes a glass of wine or beer during pregnancy. Neonatologists and paediatricians rated confidence in the ability to diagnosis FAS and FASD as low, with over 50% responders feeling they needed more information regarding FAS and FASD identification in newborn and child.Conclusions: Italian and Spanish neonatologists and paediatricians do not feel confident about diagnosing FAS and FASD. More training is needed in order to accurately diagnose ethanol use during pregnancy and correctly inform pregnant women on the consequences on the newborn.

We investigated acute and chronic exposure to environmental tobacco smoke (ETS) in a cohort of young adolescents using urinary cotinine and hair nicotine testing after recent implementation of Italian smoke free legislation. Study subjects were 372 Italian young adolescents, between 10 and 16 years of age from the principal city of Sicily, Palermo. Urine and hair samples were collected between November 2005 and May 2006, when the legislation to ban smoking in all the enclosed places of employment (including bars, restaurants, pubs) was completely enforced. An exhaustive questionnaire including sociodemographic characteristics and active and passive exposure to cigarette smoking was completed. Urinary cotinine was analyzed by radioimmunoassay and hair nicotine by a validated GC/MS method. Based on urinary cotinine results, 2.1% and 89% of the study participants, respectively, showed non-exposure and low acute exposure to ETS, whereas only 1.6% presented very high exposure or a hidden active smoking habit in the recent past. Hair nicotine disclosed non-exposure and low exposure to ETS in 11.8% and 65.6% of the young adolescents, respectively, taking into consideration a larger time-window. High repeated exposure, suggesting active smoking in some cases was observed in 8.6% of the study subjects. Hair nicotine was inversely related to educational level of the adolescents' parents. Overall, due to the implementation of smoke-free legislation and information campaign against smoking, a significant trend toward low exposure to ETS was observed in this study cohort with no association between exposure to ETS and respiratory illnesses.

Methylphenidate (MPH) is a stimulant medication widely used for treating attention-deficit hyperactivity disorder (ADHD) in children and adolescents. Therapeutic monitoring for this drug is essentially lacking and alternative biological matrices, such as oral fluid and sweat, should be investigated for noninvasive assessment of short- and long-term history of drug use. We report the excretion profile of MHP and its metabolite ritalinic acid (RA) in oral fluid and sweat from a 12-year-old boy treated with the extended release drug formulation. Concentrations of MPH and RA in oral fluid, sweat and plasma were measured by liquid chromatography-mass spectrometry. Oral fluid-to-plasma ratio at each time interval was calculated at the start of the treatment and correlated with salivary pH. Excretion of MPH in sweat patches, collected up to 24h with PharmChek patches was also investigated. MPH and RA were both detected in oral fluid with a pharmacokinetic profile similar to that in plasma. Oral fluid peak concentrations of MPH ranged between 13.5 and 30.9 ng/mL at 3.0 h after drug intake. Oral fluid-to-plasma MPH ratio between 13.1 and 3.2 demonstrated an accumulation of the drug in oral fluid. Conversely, RA was found in oral fluid at peak concentration (23.4-62.9 ng/mL) equivalent to one-tenth of those found in plasma. Concentration profiles of MPH and RA in oral fluid were quite constant during the four weeks of drug administration. In sweat, MPH was detected for the first time at 5h after drug administration (range: 9.3-11.2 ng/patch) up to 24h (range: 29.8-38.7 ng/patch). RA was not detected in the sweat patches during the 24h time of collection. The results suggest that measurement of MPH in oral fluid can be used as a potential alternative to drug monitoring in plasma. Moreover, MPH measurement in sweat patches can be used for noninvasive monitoring of MPH consumption and misuse in situations where detection of recent abuse is of interest.

HAIRVEQ is a proficiency testing program for hair analysis of illicit drugs organized by the Istituto Superiore di Sanità (Rome, Italy) and the Institut Municipal d'Investigació Mèdica (Barcelona, Spain). The aim of the three exercises performed in 2006 was the evaluation of 32 laboratories' performance when analyzing the same hair sample containing opiates, cocaine and methadone, after carrying out some specific educational interventions. In the first round, the sample was sent to be analyzed following laboratory routine methodology. In the second round, standard operating procedures (SOP) for hair testing including sample preparation, method validation and qualitative and quantitative data evaluation, and an open hair sample for SOP training were also sent together with other hair samples including the one used for performance evaluation. After the second round, a workshop was held with participant laboratories to discuss methodological issues and interpretation of obtained results. An additional amount of open samples was distributed to the laboratories for implementing the SOPs. In the third round, the same unknown sample containing opiates, cocaine and methadone was resent for the final evaluation of laboratory performance. In the first round, 11 incorrect qualitative results (10 false negative and 1 false positive) were reported by seven laboratories (22%), in the second round, a reduction in the number of incorrect results was observed (4 false negatives and 1 false positive were reported by four laboratories, 13%) and in the third round, 5 false positives and 5 false negatives were reported by seven laboratories (22%). Concerning quantitative results, the scatter was similar between the three rounds and similar to the ones reported by other proficiency tests in hair analysis. More educational actions should be addressed to a group of laboratories, which did not yet show satisfying qualitative and quantitative results.